Practical transfusion medicine for dogs and cats (Proceedings)

Veterinary transfusion medicine practices have evolved considerably over the last 10 years as we have come to better understand immunology, infectious disease, and the appropriate use of blood and blood products. Some of our biggest advances in ensuring the provision of a safe blood product has come as a result of our errors including, but not limited to acute immunologic transfusion reactions and delayed non-immunologic transfusion reactions (infectious disease transmission). The following manuscript will provide the reader with some of the keys to providing a safe blood product to dogs and cats in need.

Selecting Canine Donors Based on Blood Type:

Dog Erythrocyte Antigens (DEA) are glycolipids and glycoproteins on the surface of the red blood cell. The presence or absence of these DEA defines the blood type of an individual. The blood type of the "universal" canine blood donor varies dramatically based on individual theory, laboratory investigation, clinical experience, or a combination of these. There are two "poles" of the universal donor typing debate.

At one end of the spectrum, is the philosophy that the universal donor is one that is positive for DEA 4 (as are 98% of the population) and negative for all other DEA for which antisera (for typing) exist and negative for all anti-DEA antibody (Ab). This approach to selecting the "universal" canine donor is most likely to minimize the likelihood of an acute hemolytic transfusion reaction, maximize the lifespan of the transfused blood and make future cross match most likely to be compatible with the recipient.

At the other end of the spectrum is the theory that because DEA 1.1 is the DEA clinically implicated most often as a cause of acute transfusion reaction in previously sensitized dogs, this is the only DEA that we must routinely type for. This approach to selecting the "universal" canine blood donor will maximize the size of the donor pool.

Both blood typing systems have their advantages. For the small, private practice setting, the latter system is more economical and more practical. The author recommends performing DEA 1.1 testing on all donors and recipients. Then, only consider using DEA 1.1(-) donors OR use DEA 1.1(+) donors for DEA 1.1(+) recipients and DEA 1.1(-) donors for DEA 1.1(-) or 1.1(+) recipients. Crossmatching is not necessary for the initial transfusion. If additional transfusions are necessary >3-7days later, cross-matching procedures are indicated. Further screening is required to minimize the likelihood of infectious disease transmission.

Additional Testing of Canine Donors:

Numerous selection factors other than blood type are critical to ensuring the safety of canine blood transfusions. Screening for these factors can be somewhat time-consuming and costly; however, if it prevents morbidity or mortality to the donor or the recipient, then the increased effort is well worth the added time and expense. The author's transfusion medicine program follows the 2005 ACVIM Recommendations for Canine and Feline Blood Donor Screening for Infectious Diseases1 . Pitbull dogs and Foxhounds should be considered for exclusion from the donor program due to the relatively high incidence of Babesia sp. and Leishmania sp. respectively. Alternatively, these diseases can be screened for intensively in those breeds. In addition to being free from infectious disease, potential donors should be less than 8 years of age, have a normal CBC, Serum Biochemical Profile, and Urinalysis, no previous medical problems, a body weight greater than 25Kg, no concurrent medications, an appropriate vaccination history, no previous transfusion history, and a personality that will allow for sustained restraint for blood collection. The author currently also evaluates donors for von Willebrand Factor levels. All screening with the exception of blood type and von Willebrand factor level should be repeated on an annual basis.

Selecting Feline Donors Based on Blood Type:

Selection of feline blood donors based on blood type is much more straightforward than the canine system. Cats have three possible blood types: A, B, and AB. Unlike dogs, cats possess strong naturally occurring antibody to the opposite blood type. Consequently, inappropriate transfusion of Type A blood into a Type B cat will result in death. Transfusion of Type B blood into a Type A cat will result in an acute hemolytic transfusion reaction, but will probably not be fatal. Feline blood typing is available through commercial laboratories or via an available point-of-care test. More recently, a new feline erythrocyte antigen designated Mik has been identified to which naturally occurring antibody also appears to exist in Mik (-) cats. Mik (-) cats may develop acute hemolytic transfusion reactions after being transfused with Mik (+) but AB compatible blood. It appears that a majority of cats are Mik (+).2 The author recommends blood typing of donor cats and recipients and crossmatching all cats prior to transfusion if the tranfusion of packed red blood cells or whole blood is not urgent. If the transfusion is urgent, only consider using Type A blood for Type A cats and only consider using Type B blood for Type B cats. Because of the presence of naturally occurring antibody in the plasma of donor cats, all cats should be blood typed prior to receiving plasma. Cats should only receive plasma from donors of the same blood type.

Additional Testing of Feline Donors:

Additional screening (beyond blood type) for feline blood donors in the Northeastern United States is similar to that utilized in dogs. Infectious disease screening should evaluate potential donors for FeLV (Ag), FIV (Ab), Mycoplasma haemofelis and haemominutum (PCR), and Bartonella spp. (PCR). Due to the behavior of FeLV and the immune response to it, the author currently screens cats initially for FeLV using an antigen test, followed by a second test after 3 months of complete isolation from other cats. Suitable donors should be FeLV negative, FIV negative, and have negative PCR for Mycoplasma spp. Donor cats should weigh greater than 5Kg, have normal CBC, Serum Biochemical Profile, and Urinalysis, no previous medical problems, no current medications, a good vaccination record, no previous transfusions, and a personality conducive to extensive handling. Regarding environment, donor cats must not have any contact with other unscreened cats, must NEVER go outside, must NEVER have contact with screened cats that go outside, and must be re-screened on a yearly basis. Generally, it is most convenient for donor cats to live in single cat households. Finally, due to the significant incidence of occult cardiomyopathy in the feline population, the author recommends echocardiographic assessment of donor cats annually as a "donor-safety" factor.

Collection of Blood for Transfusion:

Prior to blood collection, all canine and feline donors should be weighed, examined, and have a small blood sample drawn for PCV or Hgb determination. If sedation is necessary, the author routinely uses an opioid in dogs and ketamine / midazolam IV or inhalent anesthesia in cats.

The area over the jugular vein should be clipped and a surgical preparation performed. For dogs, we routinely use a commercially available closed collection system containing CPDA-1 anticoagulant. Collection in cats is generally performed using an open system consisting of syringe(s) with a 1ml CPDA-1 per 9ml of blood and a 19g butterfly catheter. Risks of bacterial contamination using an open system are significantly greater than those with a closed system. 400-450ml of whole blood may be collected from dogs and 40-50ml of whole blood may be collected from cats. On rare occasion, cats and dogs may show signs of hypovolemia after donation requiring rapid intravascular volume expansion with IV fluids. Whole blood should be used immediately if an open collection system was used. To retain clotting factor function, whole blood should be used or processed into components within 8 hours of donation. Whole blood and packed red blood cells collected into CPDA-1 from a closed collection system can be stored in a strictly temperature controlled refrigerator at 4°C for up to 35days with the addition of additive solutions to improve RBC viability. The blood bags should be turned daily.

Blood Product Administration:

Fresh Whole Blood (FWB): Veterinarians in different practice settings have varied availability of blood resources. While commercial, university, and specialty hospital blood banks offer a variety of blood products with an emphasis on component therapy, the small, general practice setting is not equipped to provide these resources. Instead, fresh whole blood, collected from a donor is often the product that is available. However, it is still critical to ensure the safety of the product through appropriate blood donor screening and collection methods. FWB contains red blood cells (RBC), coagulation factors, and albumin for oncotic support. Although present, platelet activation/utilization during the collection and administration process may render the number of functional platelets that the recipient receives as relatively low and unlikely to be able to arrest hemorrhage in animals bleeding as a result of thrombocytopenia. Fresh whole blood has a number of advantages. Fresh whole blood is often administered warm and will not contribute to the negative effects that hypothermia causes in the bleeding patient. Because (in contrast to packed red blood cells) it is warm and has a "normal" PCV, it also can be more rapidly infused. In addition, it does not demonstrate the storage lesion (decreased RBC deformability, decreased 2,3 DPG, decreased ATP, accumulation of pro-inflammatory cytokines) common to stored blood products. Finally, there are few collection and processing costs compared to blood component therapy. Fresh whole blood is an excellent resuscitation fluid for use in dogs and cats with acute blood loss in concert with standard therapies for hypovolemia. In addition, FWB can also be used to provide oxygen carrying capacity (RBC) to dogs and cats with euvolemic anemia as might be encountered in destructive processes and situations of decreased production. In these patients, however, the FWB must be infused slowly so as not to cause hypervolemia. FWB should be used with extreme caution in euvolemic anemic patients with underlying left sided cardiac disease. Fresh whole blood is useful in anemic pediatric dogs and cats requiring transfusion when only a few 5-20mL of blood is needed. In these situations, it would be wasteful to squander a whole unit of packed red blood cells.

Blood Component Therapy: While FWB offers some advantages over component therapy, especially as it pertains to its use in smaller practice settings, component therapy allows for optimal utilization of this very limited resource. When FWB is processed within 6 hours, it is separated via centrifugation into packed red blood cells (pRBCs) and fresh frozen plasma (FFP). Both FFP and pRBCs (with additive solution) have greater shelf lives than the FWB from which they were derived.

PRBCs have a shelf life of approximately 35 days and can be utilized for the management of all causes of anemia until the underlying disease has been addressed. An in-depth discussion of transfusion triggers is beyond the scope of this manuscript.

Sanguineous Blood Product Administration: Most transfusions in veterinary medicine are performed electively, however, in emergency situations like hemorrhagic shock, FWB and pRBCs can be administered as rapidly as is necessary including under pressure. Rapid infusion of citrate containing blood products in large volumes could predispose to ionized hypocalcemia. Blood and blood products should ALWAYS be delivered via a commercially available 170m blood filter. A filter with low dead space is best used in cats and small dogs receiving less than 60ml of blood or blood product. Filtration of the blood will eliminate blood clots and other large particles that could cause embolic disease in the recipient. Elective transfusion of whole blood or packed red blood cells should begin slowly (1-3ml over 5min in cats and 0.25ml/Kg over the first 30min in dogs) while monitoring for signs of transfusion reaction. If no reaction is noted, the transfusion may be delivered over 1-4 hours while intermittently evaluating for any evidence of a transfusion reaction. Recipients with underlying heart disease or other conditions that may predispose to hypervolemia should receive their transfusion slowly to avoid volume overload. Whole blood or blood products should never be infused over a period of time longer than 4 hours due to the risk of bacterial proliferation in the product.

FFP is produced from the separation of FWB via centrifugation within 6-8 hours of collection. FFP contains albumin as well as all other non-cellular components of blood including coagulation factors, anticoagulant factors, immunoglobulin, and others. FFP can be stored at -20°C for one year. FFP is useful for the management of coagulopathic dogs and cats. In the author's transfusion medicine program, FFP is generally administered to coagulopathic dogs and cats that are showing signs of hemorrhage or are scheduled to undergo an invasive procedure that could result in bleeding. FFP can be administered over <4hrs via a standard blood filter (170m) and administration set. FFP can be delivered at more rapid rates in dogs and cats that are bleeding due to coagulopathy. There has been considerable debate as to whether or not FFP is indicated in the management of pancreatitis due to the proteinase inhibitors it contains. At this time, there is no strong evidence that FFP improves outcome in dogs with pancreatitis.

Similarly, FFP is often inappropriately administered for the provision of albumin to hypoalbuminemic patients. FFP is only practical for augmenting albumin concentration in very small patients. In a 20Kg dog, 2L of FFP would be needed to raise the serum albumin by 1.0g/dL (considering no ongoing losses). The mere cost of such a practice makes it impractical and an inappropriate use of a valuable blood resource that would be better utilized in a coagulopathic patient. It is the author's opinion that oncotic pressure is most practically augmented through the administration of synthetic colloids such as hetastarch. When additional oncotic support is needed beyond that provided by hetastarch, albumin transfusion is best provided through a serum albumin product.

Human Serum Albumin (HSA) has been administered to dogs because of the relative conservation of the albumin molecule across species. The results of HSA use in dogs have been very mixed. Some dogs have demonstrated fatal delayed hypersensitivity reactions. The author feels that the risks of utilizing this human product far outweigh the potential benefits. Concentrated canine and feline albumin products are reaching the market place at this time.

Frozen Plasma (FP) is FFP that has undergone >1yr of storage. It lacks certain labile coagulation factors, but does contain other plasma proteins such as albumin and various immunoglobulins.

Cryoprecipitate (CRYO) is produced from the slow thawing and centrifugation of FFP. CRYO contains concentrated VIII, von Willebrand Factor, (factor I), and fibronectin. This product can then be stored for up to a year. CRYO is useful in the prevention (prior to surgical intervention) or treatment of bleeding in dogs with von Willebrand Factor deficiency, Hemophilia A (Factor VIII deficiency), and hypo/dysfibrinogenemias. CRYO has a shelf life of one year when stored at -20°C. While FFP could be utilized to meet these same needs, CRYO can meet those needs at a lower volume. Dobermans and other dogs with cardiac disease may not be able to tolerate the large volumes of FFP necessary to provide a similar dose of necessary coagulation factors and von Willebrand Factor. In addition, dogs with the aforementioned conditions don't need all of the components of FFP. Instead, they can receive the CRYO while a bleeding anticoagulant rodenticide intoxication patient can receive CRYO poor plasma (please see below) to optimally meet his needs.

Cryoprecipitate Poor Plasma is the supernatent left over from the production of CRYO. CRYO poor plasma contains the components of normal FFP with lower concentrations of von Willebrand Factor, VIII, and I. CRYO poor plasma is still useful for the management of conditions such as anticoagulant rodenticide intoxication, Hemophilia B (Factor IX deficiency), and other inherited coagulopathies. Like FFP, CRYO poor plasma can be stored for a year at -20°C.

* Significant portions of these proceedings have been previously published for various veterinary CE Conferences.

Further Reading:

1. Wardrop KJ, Reine R, et al. Canine and Feline Blood Donor Screening for Infectious Disease. Journal of Veterinary Internal Medicine 2005;19:135–142.

2. Weinstein NM, Blais MC, et al. A newly recognized blood group in domestic shorthair cats: the MIK red cell antigen. Journal of Veterinary Internal Medicine 2007;21: 287-292.